Single Course Of Antenatal Steroids Research Articles

Long-Term Outcomes of Multiple versus a Single Course of Antenatal Steroids: A Systematic Review.

Multiple courses versus a single course of antenatal corticosteroids (ACS) have been associated with mild respiratory benefits but also adverse outcomes like smaller head circumference and birth weight. Long-term effects warrant study. We systematically reviewed long-term outcomes (≥1 year) in both preterm and term birth after exposure to preterm multiple courses (including a rescue dose or course) versus a single course. We searched seven databases from January 2000 to October 2021. We included follow-up studies of randomized controlled trials (RCTs) and cohort studies with births occurring in/after the year 2000, given advances in perinatal care. Two reviewers assessed titles/abstracts, articles, quality, and outcomes including psychological disorders, neurodevelopment, and anthropometry. Six follow-up studies of three RCTs and two cohort studies (over 2,860 children total) met inclusion criteria. Among children born preterm, randomization to multiple courses versus a single course of ACS was not associated with adjusted beneficial or adverse neurodevelopmental/psychological or other outcomes, but data are scant after a rescue dose (120 and 139 children, respectively, low certainty) and nonexistent after a rescue course. For children born at term (i.e., 27% of the multiple courses of ACS 5-year follow-up study of 1,728 preterm/term born children), preterm randomization to multiple courses (at least one additional course) versus a single course was significantly associated with elevated odds of neurosensory impairment (adjusted odds ratio = 3.70, 95% confidence interval: 1.57-8.75; 212 and 247 children, respectively, moderate certainty). In this systematic review of long-term outcomes after multiple courses versus a single course of ACS, there were no significant benefits or risks regarding neurodevelopment in children born preterm but little data after one rescue dose and none after a rescue course. However, multiple courses (i.e., at least one additional course) should be considered cautiously: after term birth, there are no long-term benefits but neurosensory harms. KEY POINTS: · We systematically reviewed the long-term impact of multiple versus a single course of ACS.. · Long-term follow-up data were scant after a rescue dose and absent after one rescue course of ACS.. · In children born preterm, multiple courses of ACS were not associated with long-term benefits/harms.. · In children born at term, multiple courses of ACS were associated with neurosensory impairment.. · Preterm administration of multiple courses of ACS should be considered cautiously..

Comparison of respiratory distress syndrome amongst preterm twins (28-34 Weeks) born within and after two weeks of completion of single antenatal corticosteroid course: A bidirectional cohort study.

BackgroundThe literature on neonatal outcomes in preterm twins delivered before 34 weeks but within and after 14 days of a single initial steroid course is limited.Material and methodsThis bidirectional (226 prospective and 42 retrospectives) cohort study was performed at a tertiary care teaching hospital in South India. We compared the respiratory distress syndrome and neonatal death amongst preterm twins from 28 to 34 weeks born < 14 days (Group A, n=268) and after 14 days (Group B, n=268) of completion of a single course of antenatal steroids. We used multivariable regression analysis (log-binomial model) to adjust for confounding variables. We generated a propensity-matched score with probit regression to analyse outcomes (respiratory distress and neonatal deaths).ResultsThe two groups had significant differences in the distribution of birthweight, gestation period and mode of delivery. On adjusted analysis, the period of gestation below 33 weeks and weight below 1.5 kg had the maximum influence on respiratory and other morbidities, and weight less than 1 kg on neonatal death. [adjusted relative risk (ARR) 26.06, (95%CI=2.37-285.5), p=0.008]. On propensity scoring after matching all these variables, we found an [ARR of 2.0 (95% CI: 1.03-3.88), P=0.017] for neonatal death after 14 days of steroid injection. The ARR for respiratory distress syndrome was 1.13 in those born after 14 days of steroids, though it did not reach statistical significance.ConclusionOn propensity scoring, the steroid-delivery interval more than 14 days was associated with a significantly increased risk (ARR of 2) of neonatal death.

Efficacy and safety of antenatal steroids.

Antenatal steroids (ANS) are among the most important and widely utilized interventions to improve outcomes for preterm infants. A significant body of evidence demonstrates improved outcomes in preterm infants (24-34 wk) delivered between 1 and 7 days after the administration of a single course of ANS. Moreover, ANS have the advantage of being widely available, low cost, and easily administered via maternal intramuscular injection. The use of ANS to mature the fetal lung is, however, not without contention. Their use in pregnancy is not FDA approved, and treatment doses and regimens remain largely unoptimized. Their mode of use varies considerably between countries, and there are lingering concerns regarding the safety of exposing the fetus to high doses of exogenous steroids. A significant proportion of women deliver outside the 1- to 7-day therapeutic window after ANS treatment, and this delay may be associated with an increased risk of adverse outcomes for both mother and baby. Today, animal-based studies are one means by which key questions of dosing and safety relating to ANS may be resolved, allowing for further refinement(s) of this important therapy. Complementary approaches using nonhuman primates, sheep, and rodents have provided invaluable advances to our understanding of how exogenous steroid exposure impacts fetal development. Focusing on these three major model groups, this review highlights the role of three key animal models (sheep, nonhuman primates, rodents) in the development of antenatal steroid therapy, and provides an up-to-date synthesis of current efforts to refine this therapy in an era of personalised medicine.

Neurodevelopmental Outcome After a Single Course of Antenatal Steroids in Children Born Preterm: A Systematic Review and Meta-analysis.

To systematically review and integrate data on the neurodevelopmental outcome of children after administration of a single course of antenatal corticosteroids for threatened preterm labor. MEDLINE, Scopus, CENTRAL, and www.clinicaltrials.gov (inception to August 2014) using combinations of the terms "prenatal," "antenatal," "cortico*," "*steroid*," "betamethasone," "dexamethasone," "neurodevelopment*," "*development*," and "follow-up." We perused the references of the retrieved articles. We included randomized and nonrandomized trials reporting on the neurodevelopmental outcomes of children whose mothers were administered a single course of betamethasone or dexamethasone antenatally for threatened preterm birth as opposed to placebo or no treatment. Summary risk ratio (RR) was calculated for dichotomous data; standardized mean difference was calculated for trials that measured the same outcome but used different methods. Heterogeneity was assessed using the I statistic. Sensitivity and subgroup analyses were planned according to study design, specific steroid, and mean gestational age at birth. A single course of antenatal corticosteroids was associated with reduced risk for cerebral palsy (seven studies; treated: 390 of 5,199, untreated: 146 of 1,379; RR 0.678, 95% confidence interval [CI] 0.564-0.815), psychomotor development index less than 70 (two studies; treated: 783 of 3,049, untreated: 258 of 969; RR 0.829, 95% CI 0.737-0.933), and severe disability (five studies; treated: 1,567 of 4,840, untreated: 475 of 1,211; RR 0.787, 95% CI 0.729-0.850). Steroid treatment increased the rates of intact survival (six studies; treated: 1,082 of 2,013, untreated: 273 of 561; RR 1.186, 95% CI 1.056-1.332). Betamethasone was found to significantly decrease the risk for severe disability and increase the rate of intact survival. Dexamethasone increased the rate of intact survival; however, data for dexametasone and the other planned subgroup analyses were limited (fewer than 1,000 children at most). The major limitations involved inclusion of nonrandomized studies and scarcity of data on finer neurodevelopmental outcomes. A single course of antenatal corticosteroids in women at high risk for preterm birth appears to improve most neurodevelopmental outcomes in offspring born before 34 weeks of gestation.

Single course of antenatal steroids did not alter cortisol in preterm infants up to 18 months

To determine whether a single course of antenatal dexamethasone alters resting cortisol at 3, 8 and 18 months corrected age in preterm infants. Preterm infants born ≤32 weeks gestational age were recruited during 2001-2004 from a single neonatal intensive care unit. Resting salivary cortisol was collected at least once at 3, 8 and 18 months corrected age in a longitudinal cohort. A mixed-effects repeated measures analysis was used to accommodate cases with less than complete follow-up. One hundred and thirty three infants were included in the present study, contributing 266 cortisol samples. Of these, 107 infants had been exposed to a single course of antenatal dexamethasone and 26 not exposed to antenatal steroids. There was no significant main effect of antenatal steroids on resting cortisol at any age. This result was not altered after adjusting for gestational age at birth, neonatal cumulative pain, morphine exposure, mechanical ventilation days and post-natal steroid exposure. No effect of a single course of dexamethasone on resting salivary cortisol, an indicator of hypothalamic-pituitary-adrenal axis function, was found in infancy up to 18 months corrected age in infants born very preterm.

European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants-2010 update

Despite recent advances in the perinatal management of neonatal respiratory distress syndrome (RDS), controversies still exist. We report the updated recommendations of a European panel of expert neonatologists who had developed consensus guidelines after critical examination of the most up-to-date evidence in 2007. These updated guidelines are based upon published evidence up to the end of 2009. Strong evidence exists for the role of a single course of antenatal steroids in RDS prevention, but the potential benefit and long-term safety of repeated courses are unclear. Many practices involved in preterm neonatal stabilisation at birth are not evidence-based, including oxygen administration and positive pressure lung inflation, and they may at times be harmful. Surfactant replacement therapy is crucial in the management of RDS, but the best preparation, optimal dose and timing of administration at different gestations is not always clear. Respiratory support in the form of mechanical ventilation may also be lifesaving, but can cause lung injury, and protocols should be directed at avoiding mechanical ventilation where possible by using nasal continuous positive airways pressure or nasal ventilation. For babies with RDS to have best outcomes, it is essential that they have optimal supportive care, including maintenance of a normal body temperature, proper fluid management, good nutritional support, management of the ductus arteriosus and support of the circulation to maintain adequate tissue perfusion.

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Decreased Respiratory Compliance in Infants Less Than or Equal to 32 Weeks' Gestation, Delivered More Than 7 Days After Antenatal Steroid Therapy

Our objective was to compare the pulmonary function (respiratory compliance) of infants who were < or = 32 weeks' gestation and delivered > 7 days after a single course of antenatal steroids versus infants who were delivered 1 to 7 days after a single course of antenatal steroids. A prospective cohort study of respiratory system compliance was conducted of infants < or = 32 weeks' gestation within 72 hours of life and before surfactant therapy if needed. The study (remote) group was composed of infants who were treated with antenatal steroids > 7 days before delivery and the comparison group (ideal group) of matched infants who were treated with antenatal steroids 1 to 7 days before delivery. Respiratory system compliance was measured with the single-breath occlusion technique. Twenty-eight remotely treated infants and 28 ideally treated infants were studied. The remote group had a significantly lower respiratory system compliance per kilogram and total respiratory system compliance when compared with the ideal antenatal steroids group. Within the remote group, infants who received antenatal steroids 8 to 14 days (n = 10) before delivery had a significantly higher respiratory system compliance and a trend to less surfactant need (10% vs 33%) as compared with infants who received antenatal steroids > 14 days (n = 18) before delivery. Infants who were < or = 32 weeks' gestation and remotely treated with antenatal steroids (average 21 days) had a significantly lower respiratory compliance compared with matched infants who were ideally treated with antenatal steroids. We speculate that the lower respiratory system compliance may reflect the dissipation of beneficial effects of antenatal steroids on pulmonary function when delivery occurs > 7 days after therapy and particularly when therapy is > 14 days before delivery.

Does time interval between antenatal steroid administration and delivery affect neonatal outcomes in very low birth weight neonates—A cohort study

DELIVERY AFFECT NEONATAL OUTCOMES IN VERY LOW BIRTH WEIGHT NEONATESDA COHORT STUDY ALLISON GOEDEN, JEFFERY GARLAND, GAIL PECKMAN, MARGARET CARR, RICHARD PIRCON, Medical College of Wisconsin Affiliated Hospitals, OB/GYN, Wauwatosa, Wisconsin, St. Joseph Regional Medical Center, Pediatrics, Milwaukee, Wisconsin, St. Joseph Regional Medical Center, Center for Obstetrical Research and Education, Milwaukee, Wisconsin, Perinatal Medicine, Ltd., Milwaukee, Wisconsin, St. Joseph Regional Medical Center, Director-Center for Obstetrical Research and Education, Milwaukee, Wisconsin OBJECTIVE: To determine whether the neonatal benefit of a single course of antenatal steroids diminishes beyond fourteen days from administration. STUDY DESIGN: This retrospective cohort study included all women who received a complete course of antenatal steroids and delivered a living singleton between 26 and 34 weeks’ gestation between January 1999 and December 2004. Maternal charts were reviewed to obtain histories and confirm treatment. Neonatal demographic data and outcomes were collected prospectively and retrospectively reviewed. Individuals reviewing maternal data were blinded to neonatal outcomes. Comparisons were made between those delivering within seven days of receiving antenatal steroids and those beyond fourteen days using Student’s t-test, chi-square analysis, Fisher’s exact test and regression analysis. RESULTS: Two hundred and fifty-one patients met inclusion criteria. Patients were grouped based upon time from administration of steroids to delivery. In univariate analysis, neonates delivering greater than 14 days from antenatal steroids had higher Scores for Acute Neonatal Physiology (SNAP) (measures the severity of illness at 24 hours of life) (9.7 G 5.6 vs 7.3 G 4.4, p = 0.001). This difference remained in regression models that controlled potential confounders [RR = 1.76 (95 percent CI = 1.2, 2.5), p=0.006]. Risk of death or chronic lung disease was statistically significant in univariate analysis (17% vs 10%, p = 0.02). When corrected for potential confounders in regression analysis, statistical significance was not achieved [RR = 2.1 (95 percent CI = 0.98, 6.2), p=0.054]. There was no difference in IVH risk in either univariate (11% vs 12%, p = 0.8) or regression analysis [RR = 0.88 (95 percent CI = 0.38, 2.0)]. S118 SMFM Abstracts

The interval between a single course of antenatal steroids and delivery and its association with neonatal outcomes

This study was undertaken to determine whether the benefits of a single course of antenatal steroid treatment for neonatal respiratory morbidity diminish beyond 7 days. A retrospective chart review was performed of all deliveries less than 34 weeks' gestation where delivery occurred after completing a single course of antenatal steroids (dexamethasone or betamethasone). Maternal and neonatal charts were reviewed, treatment course was confirmed, and neonatal morbidities were collected. Of 197 neonates whose mothers received a full course of antenatal steroids, 98 delivered within 7 days and 99 delivered more than 7 days after the initial dose. The 2 groups were similar in gestational age at delivery (30 weeks 0 days vs 30 weeks 4 days). The groups were also similar in maternal age, race, payor status, type of steroid given, route of delivery, gender, and birth weight. Overall, infants delivering within 7 days had a lower incidence of receiving respiratory support for more than 24 hours (62% vs 81%, P < .01), but there were no significant differences between the groups in surfactant treatment (39% vs 47%), use of mechanical ventilation (49% vs 59%), necrotizing enterocolitis (6% vs 4%), intraventricular hemorrhage (15% vs 20%), oxygen dependence at 28 days (24% vs 23%) or at 36 weeks estimated gestational age (13% vs 12%), length of stay (34 days vs 38 days), or mortality (2 vs 0). These results were no different when evaluating only infants delivered before 30 weeks. Among infants exposed to a single course of antenatal steroids, delivering more than 7 days after initiation of treatment was associated with an increased need for short-term respiratory support, but not other measures of neonatal morbidity. These data challenge the concept of diminishing efficacy of steroids after 7 days, and question the need for considering a rescue course.

Alterations in Fetal Kidney Development and Elevations in Arterial Blood Pressure in Young Adult Sheep after Clinical Doses of Antenatal Glucocorticoids

Epidemiologic studies have yielded controversial information regarding an association between antenatal steroid administration and elevations in arterial blood pressure (BP). The aim of the study was to determine whether antenatal administration of a clinically relevant dose of steroids at a time when fetal nephrogenesis is at its highest results in abnormal kidney development and adult hypertension. Pregnant sheep were treated with either vehicle or betamethasone. Maternal injections were given 24 h apart at 80 d of gestational age (dGA; 0.55 of gestation). Animals were studied either as fetuses or as immature adults. Fetuses were delivered by cesarean section at 135 dGA. Adults were studied at 6 mo of age. Betamethasone administration did not induce premature labor or intrauterine growth restriction. In the betamethasone-exposed group, we found at 135 dGA a 25.5% decrease in the number of glomeruli with no differences in fetal kidney weight. In adults, mean, systolic, and diastolic arterial BPs were significantly higher, whereas there were no significant differences in heart rate over the same study period. The major finding of this study is that a single course of antenatal steroids alters renal development and is associated with elevations in arterial BP in lambs at 6 mo of age. We conclude that antenatal glucocorticoid administration under the National Institutes of Health consensus guidelines may alter human fetal renal development.

The efficacy of a single course of antenatal steroids beyond seven days

ALAN PEACEMAN, KOMAL BAJAJ, PRAVEEN KUMAR, WILLIAM GROBMAN, Northwestern University, Obstetrics and Gynecology, Chicago, Illinois, Northwestern University, Neonatology, Chicago, Illinois OBJECTIVE: To determine whether the benefits of a single course of antenatal steroid (AS) treatment for neonatal respiratory morbidity diminish beyond seven days from initiating treatment. STUDY DESIGN: A retrospective chart review was performed of deliveries !34 wks gestation where delivery occurred after completing a single course of AS (dexamethasone or betamethasone). Maternal and neonatal charts were reviewed, treatment course was confirmed, and neonatal morbidities were collected. A review of 190 charts provided more than 80% power for demonstrating a 50% reduction in the need for respiratory support (ventilation, CPAP) if delivery occurred within 7 days of treatment. RESULTS: Of 197 infants whose mothers received a full course of AS, 98 delivered within 7 days, and 99 delivered more than 7 days after the initial dose. The two groups were similar in gestational age at delivery (30 wk 0 d vs 30 w 4 d). The groups were also similar in maternal age, race, payor status, type of steroid given, route of delivery, gender and birth weight. Overall, infants delivering within 7d had a lower incidence of receiving respiratory support for >24 hours (62% vs 81%, P ! .01), but there were no significant differences between the groups in need for surfactant (39% vs 47%), mechanical ventilation (49% vs 59%), NEC (6% vs 4%), IVH (15% vs 20%), oxygen dependence at 28d (24% vs 23%) or at 36 weeks EGA (13% vs 12%), length of stay (34 d vs 38 d) or mortality (2 vs 0). These results were no different when evaluating only infants delivered before 30 weeks. Further, for those infants who delivered greater than 7 days after AS, there was no association between increasing time intervals after AS and neonatal morbidity. The power to observe a 50% reduction in surfactant use and mechanical ventilation was 94% and 99%, respectively. CONCLUSION: Among infants exposed to a single course of AS, delivering more than 7 days after initiation of treatment did not appear to be a disadvantage. These data challenge the concept of diminishing efficacy of steroids after 7 days, and question the need for considering a rescue course. 383 THE ASSOCIATION OF FETAL GENOTYPE FOR THE MTHFR GENE AND PRETERM PREMATURE RUPTURE OF MEMBRANES AMIE HOLLARD, RHONDA FLORA, PAMELA RUMNEY, JUDITH CHUNG, MICHAEL NAGEOTTE, University of California, Irvine, Maternal Fetal Medicine, Lincoln, Nebraska, University of California, Irvine, Maternal Fetal Medicine, Orange, California, Long Beach Memorial Medical Center, Maternal Fetal Medicine, Long Beach, California OBJECTIVE: Methylenetetrahydrofolate reductase (MTHFR) plays a role in folate/homocysteine metabolism. The common polymorphisms in the MTHFR gene are C677T and A1298C, the presence of which has been associated with adverse pregnancy outcome. Given that folate and homocysteine are involved in collagen synthesis, we hypothesize the presence of MTHFR mutations in the fetus may increase the risk for preterm premature rupture of membranes (PPROM). STUDY DESIGN: A nested case control pilot study of 2 groups. Group I (n = 18): patients with PPROM delivering between 24 and 35 weeks. Group II (n = 25): patients without PPROM delivering between 24 and 42 weeks. Patients with diabetes, hypertension, preeclampsia, or multiple gestations were excluded. At delivery, a placental biopsy was obtained. The fetal RNA was extracted and multiplex PCR/ RFLP was performed for the presence of C677T and A1298C alleles. Univariate analysis, Chi-Square, Fisher’s Exact, & unpaired t tests were used as appropriate. Significance was set at P ! .05. RESULTS: The allele frequencies for C677T & A1298C are 28% & 44%, and 48% & 44% for Group I and Group II respectively . In Group II, there was an equal distribution of of the alleles between patients delivering at ! or >34 weeks gestation. In the Caucasion patients, 100% of Group I patients and only 60% of Group II patients had one or more mutations present. However, in the combined population there was no overall increased risk of PPROM if the fetus had one or more C677T P = .31) or A1298C mutations (P = .98). CONCLUSION: In our study, it appears that the presence of fetal C677T and A1298C polymorphisms are not uniquely associated with PPROM, but it may influence PPROM in certain ethnic groups. The effect of maternal genotype was not evaluated in this study, there may be additive effect when both genotypes are considered concurrently. An unexpected finding in this study was the large number of control patients with either mutation. A larger sample size is needed to discern if a true association is found between the presence of MTHFR mutations and PPROM.

Current controversies surrounding the use of repeated courses of antenatal steroids.

The use of a single dose of antenatal steroids to facilitate fetal lung maturation in the expectant management of threatened preterm birth has significantly improved the mortality and morbidity of premature infants worldwide. In some settings, the evidence for this practice has been extrapolated with self-reports of up to 6 repeated courses during the antepartum period. Concerns about the use of repeated antenatal courses prompted the National Institutes of Health (NIH) to publish a consensus statement (2000) that reaffirmed the safety and efficacy of a single course of antenatal steroids, but emphasized that there are no data to support the safety and efficacy of repeated courses. The statement cautions against the use of multiple courses outside of research protocols. Despite these recommendations, wide variations in clinical practice continue to exist. There are growing concerns about the potential deleterious effects of steroid exposure on the developing human brain. It is plausible, although not proven, that negative neurodevelopmental impact may occur, or be compounded by multiple antenatal or combined antenatal and postnatal steroid exposures. This article provides a review of the evidence to support appropriate steroid use. The physiology and pharmacology of both endogenous and exogenous steroids are outlined to enhance the clinician's understanding of these potent agents. Recommendations for targeted clinical evaluation and short- and long-term follow-up of steroid exposed infants are provided. A clear understanding of the known and potential risks and benefits of single and multiple courses of antenatal steroids is essential to prompt a critical re-examination of the safety and efficacy of repeated steroid exposure in the neonate.

Antenatal therapies and the developing brain

This chapter presents a review of basic science and human studies of two commonly used pharmacologic agents (antenatal steroids and magnesium sulfate), in pregnancies at risk of preterm delivery, and examines the effects of these therapies on the developing brain. Very low birthweight (VLBW) infants are known to be at risk of both short-term and long-term neurodevelopmental sequelae; therefore, an understanding of the mechanisms contributing to both neuroprotective and neurotoxic effects of antenatal therapies on the immature brain and potential effects on long-term outcome are critical. Although the short-term beneficial effects of a single course of antenatal steroids are well documented, the experimental animal literature suggests detrimental effects on neurodevelopment of multiple doses. In addition, clinical studies of repeat doses suggest a negative impact on head and brain growth. The animal and human data on the effects of MgSO4are also mixed with both beneficial effects or no effects on neurodevelopment. This review will discuss the potential impact of single versus multiple doses and timing of doses on the brain.